NEEMA Funded Projects by Topic Area – Viral Hepatitis

In the United States, testing for hepatitis C virus (HCV) infection currently involves a two-step diagnosis process that is dependent on antibody testing, which can lead to underdiagnosis in populations with ongoing transmission. Current requirements for a prior test detecting HCV antibodies may be problematic in settings that test persons at higher risk for recent exposure/acute infection, such as syringe services programs and substance use treatment facilities, and for immunocompromised persons who may not have a reactive HCV antibody test. This project will assess the cost-effectiveness of one-step HCV testing versus the two-step HCV testing process to determine the best approach for early and reliable diagnosis of HCV infection.

Hepatitis C virus (HCV) infection is the most reported bloodborne infection in the United States despite being underreported. An accurate estimate of hepatitis C prevalence can inform public health interventions and resource allocation strategies aimed at reducing the health burden and economic costs caused by hepatitis C in the United States and inform progress toward the global goal of eliminating viral hepatitis as a public health problem by 2030. The most recently available national HCV prevalence estimate in the United States is based on data from 2013–2016. This project will generate an updated estimate of HCV prevalence among the adult (≥18 years) US noninstitutionalized civilian population using 2017-2020 data from the National Health and Nutrition Examination Survey (NHANES) and compute additional prevalence estimates for populations that are not part of the NHANES sampling frame (e.g., incarcerated people, unsheltered homeless people, active-duty military personnel, and nursing home residents).

Previous efforts toward HCV elimination within state Departments of Corrections have included a combination of guidelines and evidence, as well as legal pressure. To sustain momentum in states where action has been taken and to initiate HCV elimination strategies in other states, it is helpful to estimate across states what would be the likely costs and health benefits of universal HCV testing and treatment strategies in prisons. This project assesses the potential health and economic implications of broad strategies toward universal HCV testing and treatment in prisons.

Hepatitis B disproportionately affects some populations, and in the United States it disproportionately affects both native and immigrant Asian and Black populations. This project builds on previous Prevention Policy Modeling Lab’s work to evaluate the hepatitis B care cascade In the United States using insurance data, which showed that Asian patients and patients with commercial insurance were more likely to receive monitoring and treatment than other patients. This project will evaluate the impact of reducing racial and insurance disparities in the hepatitis B care cascade to inform policymakers on the impact of these efforts to improve equity.

Hepatitis D is the most severe form of viral hepatitis, with faster disease progression to cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related death. Hepatitis D virus (HDV) needs the hepatitis B surface antigen from hepatitis B virus (HBV) to propagate and cause disease. A recent National Health and Nutrition Examination Survey (NHANES) study reported an anti-HDV prevalence of 42% among hepatitis B surface antigen positive (HBsAg) carriers. Due to the fast disease progression rates and lack of therapy, hepatitis D remains neglected. However, new therapies for HDV may soon become available. The American Association for the Study of the Liver Disease recommends testing persons who are HBsAg-carriers and at high risk for HDV infection. This project aims to evaluate the estimated effects of universal HDV screening of adult HBsAg-positive persons compared to persons at high-risk (status quo), by calculating costs, quality adjusted life years, and health outcomes, as well as evaluate potential cost-effectiveness of new therapies, when available.

Only a fraction of hepatitis A, acute hepatitis B, and acute hepatitis C cases are reported through the National Notifiable Disease Surveillance System to CDC. There are several barriers to ascertaining and reporting acute infections, including the fact that many people with viral hepatitis infections may not develop symptoms, may not seek care if they become symptomatic, or may not be reported to public health authorities if they do receive medical care. Currently, CDC estimates the incidence of viral hepatitis A, B, and C infections using three probabilistic multiplier models. This project will update and improve the methodology used to estimate the incidence of acute viral hepatitis cases in three key ways. First, it will upgrade the structural model to a hierarchical framework and include covariates that can predict variation in each of the three adjustment factors (i.e., probabilities of symptoms, care-seeking, and capture in the surveillance system). Second, it will incorporate time series and stratum-specific estimates of underlying incidence and corresponding case notification data. Finally, it will focus on joint modeling of hepatitis A, B, and C incidence, including ascertainment and reporting, with synthesis of available evidence relevant to each and accounting for shared processes.

As of October 2019, widespread hepatitis A virus (HAV) outbreaks were ongoing in 30 states due to person-to-person transmission, resulting in more than 27,000 reported cases, and 275 deaths. Key populations at increased risk of infection are people who use drugs (PWUD), people experiencing homelessness (PEH), and men who have sex with men (MSM). Local health departments urgently require information on levels of vaccination needed to prevent outbreaks and achieve herd immunity. Previous studies estimating target vaccine coverage required to prevent HAV outbreaks have been limited to endemic transmission and universal vaccination as opposed to targets for specific populations at increased risk. This work will combine the state-level and national data on HAV outbreaks with dynamic modeling to understand herd immunity thresholds among, and transmission patterns between, PEH, PWUD, and MSM. Developing a tool for counties to use to estimate required vaccination numbers and the associated vaccination budget is also planned.

The most recent CDC hepatitis B screening recommendations were published in 2008. Since then, additional groups at increased risk (people co-infected with hepatitis C, people with current or history of sexually transmitted infections, people with current or history of incarceration) and testing strategies (HBsAg only; anti-HBc followed by HBsAg if anti-HBc-positive; HBsAg and anti-HBs; or HBsAg, anti-HBs, and anti-HBc) have emerged. Cost-effectiveness analyses for hepatitis B testing strategies in populations at increased risk will help inform the next CDC testing recommendations. This project will estimate the cost-effectiveness of hepatitis B testing in people with a history of or current STIs, a history of or current incarceration, or co-infection with hepatitis C, and will examine the cost-effectiveness of universal screening for people born before 1991 (time when universal hepatitis B vaccination recommendation was implemented). For each group, it will assess the cost-effectiveness of different testing algorithms based on various combinations of the 3 HBV seromarkers (HBsAg, anti-HBs, and anti-HBc).

CDC and the U.S. Preventive Services Task Force recommend one-time routine hepatitis C virus (HCV) screening for all adults (18 years and older). CDC continues to recommend that people with risk factors be tested regularly, such as people who inject drugs. However, there is no evidence to inform the optimal testing interval for people at increased risk, or the cost and cost-effectiveness of intensive and frequent testing. This project will use a previously developed agent-based network model of HCV transmission across injection-drug-using networks to: 1) identify the minimum HCV testing frequency needed to achieve HCV elimination among persons who inject drugs (PWID), 2) estimate the cost of such testing and treatment, and 3) measure the cost-effectiveness of various testing frequencies.

As an increasing number of states begin to tackle state-wide hepatitis C elimination plans, the success of these initiatives is likely to depend on effectively addressing the high prevalence of hepatitis C virus (HCV) infection and its risk factors in correctional populations, including jails and prisons. Previous studies focused on evaluating a range of strategies for HCV testing and treatment in prisons and found that such strategies could provide high value for funds invested. Jails differ from prisons in several ways that present logistical and cost challenges for scaling up HCV testing and treatment. Jail sentence durations are typically short, meaning that most people who initiate HCV treatment in a jail will need to be linked to a treatment provider in the community upon release. Jails typically do not have available resources to support large-scale HCV treatment, or adequate infrastructure for monitoring patients and linking them to community care. This project will focus on optimizing HCV testing and treatment strategies in jails and the associated clinical and public health benefits of different strategies by identifying testing and treatment implementation models that provide good value for the resources invested in scale-up and then estimating budgetary impact from the jail perspective.

In the United States, injection is an increasingly common and high-risk route of administration for prescription and illicit opioids as well as other drugs such as methamphetamine. Unsafe injection drug use (IDU) behaviors increase risk for bloodborne infectious diseases such as HCV and HIV, making these infectious diseases secondary but deleterious consequences of the opioid crisis for people who inject drugs (PWID). Due to the stigmatized and illicit nature of non-medical IDU, population-level prevalence is difficult to measure using survey methods typically used to monitor health-related behaviors. Estimation of national population size of PWID is critical for informing infectious disease prevention efforts among PWID. The current national PWID population size estimate is based on household survey data from 2011 and does not reflect current opioid and methamphetamine injection. This project will update the PWID prevalence estimates nationally and for specific subpopulations of interest.

Persons who inject drugs (PWID) are at high risk for multiple bloodborne and sexually transmitted infections, including hepatitis C virus (HCV) and HIV. National and state-level planning for SSPs and MOUD relies on the accurate estimation of PWID population size and requires an understanding of how these interventions impact HCV and HIV transmission, in addition to other bloodborne infections, among this subpopulation. The particular structure of injection networks and sexual networks among PWID leads to heterogeneous risks of infection transmission and acquisition across the subpopulation. In addition to SSPs and MOUD, many other preventive strategies are available for both HCV and HIV, including biomedical interventions (e.g., HIV pre-exposure prophylaxis, HIV treatment, HCV treatment) and behavioral interventions (e.g., promoting safer injection practices, condom use). Interventions can interact with each other and generate synergistic (or antagonistic) effects on the prevention of HCV and HIV. What determines the optimal intervention package is unknown. This project will extend our existing agent-based network model of HCV transmission among PWID by adding the sexual partnership network and transmission dynamics of HIV and other sexually transmitted infections to the existing network of equipment-sharing, to: (1) determine the levels of SSP coverage needed to reduce new HIV and HCV infections among PWID by 25%, 50% and 90%; (2) compare the population health and economic impacts of different levels of program coverage for opioid use disorder; (3) identify intervention combinations among the different prevention strategies that may produce substantial reductions in HCV and HIV burden among PWID; and (4) compare the cost-effectiveness of different intervention packages.

There are limited data and literature that describe the cascade of care for HBV infection in the United States. Past studies suggest many people with hepatitis B are not aware of their infection and that those who are eligible, are not receiving care and treatment. This project will collect up-to-date data on the hepatitis B cascade of care and evaluate the cost-effectiveness of improvements. Health system datasets will be used to better understand rates of, and costs of, screening, linkage to care, and treatment for those who are eligible. Modeling tools will be used to understand the current cascade of care for hepatitis B in the United States and evaluate the cost-effectiveness of portfolios of interventions to improve and increase rates of screening, linkage to care, and treatment for those who are eligible.

Moving toward elimination of hepatitis C virus (HCV) infection in the United States will require achieving several targets for the HCV care cascade, such as diagnosing 90% of people living with chronic HCV infection, linking 90% of those diagnosed to care, and treating 80% of those for whom treatment is indicated. This project builds on previous NEEMA projects that used the hepatitis C cost-effectiveness simulation model to inform CDC screening guidelines and intervention policies to examine HCV elimination strategies in correctional settings and in the community. This project will explore a range of different public health strategies that can improve the HCV care cascade, such as enhanced surveillance, expanded screening in key venues (e.g., correction settings, primary care clinics, emergency departments), and integration of programs and services related to the opioid use epidemic. Furthermore, the project will evaluate the costs associated with these public health interventions and capacities and quantify the return on these investments in terms of both health and economic outcomes.

The Advisory Committee on Immunization Practices currently recommends vaccination against hepatitis B for all infants as well as for adults with risk factors for infection. However, complete series coverage among adults remains low. Traditionally, vaccination against hepatitis B infection is a 3-dose series given over the course of six months. Recently, a 2-dose HBV vaccine that can be completed in one month was licensed for use in adults. This 2-dose regimen could result in higher vaccination completion rates (compared with the 3-dose series), especially among individuals in high-risk settings. The objective of this project is to assess cost-effectiveness of using a 2-dose versus 3-dose HBV vaccine in a variety of settings that serve people at high risk for HBV infection, such as STD clinics, TB clinics, substance use disorder clinics, syringe service programs, jails, and HBV testing and vaccination outreach events in communities with large immigrant populations. The project will use a decision tree analytic model to compare a 2-dose vaccination strategy to a 3-dose vaccination strategy in each setting of interest.

The COVID-19 pandemic is likely to increase HIV and HCV infection risk among persons who inject drugs (PWID) due to potential changes in injection behaviors and limited availability of harm reduction services. Frequency of injection, type(s) of drugs injected, sharing behaviors, and HIV/HCV testing behaviors may all change to some extent amid disruption of the drug supply, existing social networks, and harm reduction services. This project aims to understand COVID-19-related changes in the health risks of PWID. Multi-level impacts on PWID health will be considered, such as housing instability, access to syringe services programs (SSPs), sharing behaviors, and HIV/HCV testing behaviors.

Over the past decade, acute HCV incidence rates have been increasing and are highest among adults of reproductive age. As a result, the number of infants with perinatal exposure to HCV is also increasing. Neither CDC nor the US Preventive Services Task Force has published testing recommendations for infants perinatally exposed to HCV and other recommendations from medical organizations are inconsistent and confusing for clinicians – leading to a lack of testing among HCV-exposed children and resulting in many undiagnosed pediatric HCV infections. This project’s objective is to use an economic analysis framework to identify the optimal testing strategy for infants born to HCV-infected mothers.

Persons who are inactive hepatitis B carriers (defined as HBsAg-positive, HBeAg-negative, normal levels of alanine aminotransferase (ALT)<40 U/L and HBV DNA <10,000 copies/m) make up the largest group of persons with chronic hepatitis B virus (CHB) infection. Treatment is not recommended for this group, since there is not enough evidence on whether current antiviral therapy affects HBsAg status in the long-term. Patients transition from inactive to active (become eligible for treatment) at a rate of 0.9% – 2.0% annually, depending on their age. Treatment guidelines suggest that inactive CHB should be monitored for ALT and HBV DNA levels. Despite these recommendations, the uptake of lifelong monitoring of ALT and HBV DNA among those that are on and off treatment – as well as hepatocellular carcinoma surveillance – is low or even nonexistent. This project will assess the cost-effectiveness of a strategy of lifelong monitoring for inactive chronic hepatitis B virus and treatment of eligible patients in the United States.

Responsible for an estimated 1.3 million deaths each year, viral hepatitis is a leading cause of mortality globally. The majority of hepatitis-related morbidity and mortality results from chronic hepatitis B virus (HBV) infections, which number an estimated 257 million. Hepatitis B vaccination of children was introduced globally in the 1990s, and coverage reached 84% by 2015. Efforts to accelerate prevention and treatment of HBV infection globally were made in 2016 with the launch of the Global Health Sector Strategy (GHSS) on viral hepatitis, which calls for the elimination of viral hepatitis as a public health threat by 2030. In 2016, nearly 1.2 million people obtained lawful permanent resident status in the United States; approximately 157,000 of whom had refugee/asylee status. Close to 800,000 of these immigrants were born in Asia or Africa, where 68% of those living with HBV infection reside. The impact of global efforts to prevent and treat HBV infection on the burden of HBV infection among immigrants entering the United States is unknown, as are the potential cost savings for the health care system. This project assesses the impact of global efforts to prevent and treat HBV infection on the burden of chronic HBV infection in the United States.